The objectives of this grant are threefold. The first is to further define the breadth and function of citrate usage in eye disease. To this end citrate will be used topically in two other conditions characterized by PMN infiltration and ulceration, vitamin A deficiency and bacterial corneal ulcers in albino rabbits. Since the major mechanism of action of citrate is PMN inhibition by calcium chelation, the topical use of calcium citrate should not have any demonstrable effect on the prevention of corneal ulceration after alkali injury. An array of in vitro assays on PMN activities will determine if new, metalloproteinase inhibitors interfere with PMN functions. Aim two will establish which corneal layers make a greater contribution to production of the chemoattractant after alkali-injuries. The primary sequence of the chemoattractant will be uncovered and compared to a series of synthesized tripeptides which are analogues of the alkali-degraded chemoattractant. The inactive tripeptide analogues and other "designer" inhibitors of both the PMN receptor and the chemoattractant, will be studied. Our last aim investigates the injection of the inflammatory mediators into the normal cornea. Crude extract from the alkali-degraded cornea, purified chemoattractant and respiratory burst fractions or the synthetic chemoattractant, will be injected intrastromally to mimic the inflammatory response occurring in the alkali-injured eye. A variety of known compounds which decrease the incidence of ulcers in alkali- injured animal models and other compounds known to inhibit the chemoattractant will be used to attempt to alter these inflammatory reactio .